This proposal focuses on the differentiation and activation of the mouse B lymphocyte lineage. Extensive use will be made of B cell progenitor-reconstituted investigate the in vivo regulation of B cell differentiation by T cells and other cell types. The sites of localization and the functional capacity of B cells generated in this adoptive transfer model will be determined. The role of the Lyb-2 surface molecule in the regulation of early B cell differentiation will be evaluated. A large fraction of newly- formed B cells fail to survive for more than 24-48 hours, and we will evaluate hypotheses regarding the mechanism of this cell death. We will examine the effect of antigen or anti-idiotypic stimulation on the survival of newly emerging specific B cells and on the relative expression of different antibody specificities. We also will continue to study the details of T cell:B cell collaboration during the course of in vitro antibody responses. Our previous evidence suggests that prolonged T:B contact is required for the induction of antibody synthesis by small B cells, and we will perform experiments that involve disruption of T:B conjugates formed between cloned helper T cells and immunoglobulin transgenic B cells to determine the duration and importance of these interactions. These experiments will use mice as the experimental animal, and should yield important new information on the control of B cell differentiation, the relationship of various B cell subsets, and the mechanism of T:B cell collaboration.